Our lab's interest can broadly be divided into two categories.

i. Investigating mechanism of mismatch repair (MMR) deficiency in solid tumors. Primarily, our lab is interested in discovering genetic causes of early-onset colorectal cancer. Specifically, we focus on understanding the disease mechansim in patients who present with tumors exhibiting clinical hallmarks of mismatch repair deficiency, yet lack diagnostic proof of hereditary pathogenic changes in the canonical MMR genes or their sporadic inactivation. These patients are categorized as having an unexplained mismatch repair deficiency (uMMRd) or Lynch-like syndrome (LLS). A molecular explanation for LLS patients is often absent. We aim to identify genes which are of diagnostic significance for LLS-suspect patient population.

This work is currently supported by the Chris4Life Colorectal Cancer Alliance Early Career Investigator Award Grant.

ii. Facilitating CRISPR based functional genomics approaches to allow high throughput precise  gene editing. This primarily involves modulation of intrinsic DNA repair pathways to allow highly efficient targered edit either by use of inhibitors or augmentation with biological modulators.

My current research focuses on modeling Lynch syndrome (LS)/Lynch-like syndrome (LLS) associated gene variants in human embryonic stem cells using CRISPR-Cas gene editing. We aim to gather variant specific functional data to better inform the clinical diagnosis and stratification of LS/LLS patients. 

Over the course of the last few years, we have optimized CRISPR based genome engineering to serve as a highly efficient tool to site-specifically incorporate genomic single nucleotide variant change. We aim to improve the throughput of this powerful reverse genetic approach for large scale functional genomics studies and lessen the existing technical constraints. Specifically, we aim to explore novel methodologies to improve homology directed repair outcomes for CRISPR-Cas induced DNA double-strand breaks. 

We also aim to study the putative genetic modifiers of mismatch repair by modeling them in human cells and functionally evalutate them for preservation of mismatch repair function.

i. Hereditary basis of unexplained MMR deficiency

Journal Articles